We are studying in culture two biochemically and morphologically distinct populations of bone cells, CT cells and PT cells that respond in distinctly different manners to parathormone an calcitonin. The parameters measured (and the cell type in which parathormone produced a change) are: acid phosphatase, hyaluronate synthesis, mineral and matrix resorption from dead bone (CT cells); alkaline phosphatase, citrate decarboxylation, prolyl hydroxylase, collagen synthesis and hydroxylation (PT CELLS); cAMP (CT and PT cells). On the basis of the basal activities and hormone-induced changes the CT cells have been identified as osteoclasts and/or osteocytes and the PT cells as osteoblasts. We are further characterizing these bone cells by determining their growth and development in culture, the sites where they existed in situ prior to removal from the calvaria and the degree of heterogeneity of the isolated populations. We plan to study the biochemical changes induced by parathromone and other bone-active hormones in normal and genetic mice (osteopetrotic) in order to better realize the biochemical bases for these alterations. Finally, we will measure the binding and interaction of parathormone and other agents with the isolated bone cells and bone-cell membranes.